This research application has three specific aims that, if successful, will result in a more accurate staging of the breast cancer patient and have direct impact on present day patient care. The current staging procedure for breast cancer involves one of the definite surgical procedures for the disease, either lumpectomy, axillary dissection and radiation therapy to the rest of the breast of a standard modified radical mastectomy. From the pathological examination of these tissues, patients have their primary disease controlled and are placed into either "high risk" or "low risk" for recurrence groups in order to direct subsequent adjuvant therapy, consisting of either a 6 month course of chemotherapy, long term Tamoxifen or both. Event though the adjuvant therapies have side effects and risks associated with them, it is safe to say that almost all women with invasive breast cancers will get come form of adjuvant therapy. In fact, it is the community standard that all pre-menopausal women with an invasive breast cancer over 1.0 cm receive 6 months of cytotoxic chemotherapy. This non- selective approach has caused some experts in the field to recommend not doing axillary node dissections, at all, if the staging information gained is not going to have an impact on the decision for adjuvant treatment. A better approach to the staging of the breast cancer patient would be to gather the staging information from the histologic examination of the axilla with minimal invasive procedures that carry little if any morbidity. From previous work from our laboratory with lymphatic mapping and sentinel node harvesting in melanoma, it is clear that there is an orderly progression of metastatic disease for melanoma. That is, if the sentinel node, defined as the first node in the lymphatic basin into which the primary site drains, is negative for metastatic disease, then the rest of the nodes in the basin should also be negative. Thus, with a simple lymph node biopsy, all the staging information of a complete axillary dissection becomes available. Pre-operative lymphatic mapping (lymphoscintigraphy), intra-operative lymphatic mapping (Isosulfan Blue, Technitium Human Serum Albumin and the Neoprobe) and sentinel node identification will be followed by the standard axillary dissection that accompanies either a lumpectomy or modified radical mastectomy to treat primary invasive breast cancer. Lymphatic mapping and sentinel node biopsies will be performed in patients with invasive breast cancers to (1) document the incidence of skip metastases in breast cancer, (2) examine lymphatic drainage patterns from breast caners in various quadrants of the breast, (3) apply a highly sensitive polymerase chain reaction (PCR) technique for the identification of occult metastases and compare this technique with routine histology, and (4) attempt to document clinical correlation with the finding of occult metastases with the PCR technique.